Antimicrobial Articles

ABSTRACT

Advantageously, para-chloroaniline (PCA) is minimal in antimicrobial articles prepared according to the method of the invention. A method of forming an antimicrobial article according to the invention comprises steps of: providing a polymerizable composition; incorporating an antimicrobially effective amount of at least one chlorhexidine-containing antimicrobial agent into the polymerizable composition; and, polymerizing the polymerizable composition to form chlorhexidine-containing polymer of the antimicrobial article, wherein processing temperature during the method is less than about 80° C.

BACKGROUND OF THE INVENTION

The present invention relates generally to methods of processingchlorhexidine-containing polymerizable compositions and antimicrobialarticles formed thereby.

The United States' Center for Disease Control (CDC) recommendschlorhexidine gluconate as the preferred skin antiseptic over tincturesof iodine, iodophors, and alcohol. Chlorhexidine, a substituteddiguanide, has a high degree of antimicrobial activity, low mammaliantoxicity, and the ability to bind to the stratum corneum layer of skinand to mucous membranes. The bactericidal activity of chlorhexidine ismuch greater than that of monomeric biguanides. These uniquecharacteristics make it particularly attractive as an active ingredientin antimicrobial skin preparations. Besides its use in specific medicaldressings and skin antiseptics, the efficacy of chlorhexidine inproviding antimicrobial protection is known further throughout themedical industry. However, when incorporated into polymerizablecompositions, elevated processing temperatures are often used, which canpotentially damage the chlorhexidine within.

An example of such elevated temperature processing is described in U.S.Pat. No. 5,165,952, where a temperature range of 160° C.-250° C. isused. Referencing the same, U.S. Pat. No. 8,383,143 states: “Whenchlorhexidine is bulk distributed it adversely affects certaincharacteristics of the device such as tensile strength, and the hightemperatures needed for extension of plastics such as polyurethane maydamage the chlorhexidine.” U.S. Patent Publication No. 2013/0303656similarly references the negative effects associated with processingchlorhexidine-containing materials at elevated temperatures.

Not only does processing at elevated temperatures potentially decreaseefficacy of chlorhexidine-containing articles, but it is also known tocreate a toxic chemical. Hydrolysis of chlorhexidine yieldsp-chloroaniline (also referred to as 4-chloroaniline, but referred tohereinafter as PCA). The amount of PCA generated is relativelyinsignificant at room temperature, but becomes more significant astemperature is increased by heating, especially at alkaline pH. Attemperatures of about 40° C. or greater, chlorhexidine is documented asdecomposing to PCA, as described in, for example, Ranganathan, N. S.(1996), “Chlorhexidine,” in Ascenzi, Joseph M. (Ed.), Handbook ofAntiseptics and Disinfectants, Marcel Dekker, Inc. (New York), pp.235-265. Thus, when thermal processing of chlorhexidine-containingarticles is employed, introduction of PCA therein has been unavoidable.

Many polymer-based materials are processed at elevated temperatures. Forexample, see U.S. Patent Publication No. 2011/313048, which describes anantimicrobial silicone-based wound dressing formed from a liquidcontaining silicone and employing particulates of a chlorhexidinecompound that is not soluble in the liquid, where processingtemperatures of 100° C.-150° C. are described. In general, continuousweb-based processing of polymerizable compositions often occurs attemperatures of 80° C.-100° C. Thus, decomposition of chlorhexidineincorporated therein to PCA is not only prevalent along the length of amoving web when subjected to such continuous processing, but it becomeseven more so at locations along the web that were halted duringprocessing, which often occurs and often involves excess exposure timeto heating elements positioned along the web.

In view of the toxic nature of PCA, desired are new methods ofprocessing chlorhexidine-containing polymerizable compositions andantimicrobial articles formed thereby, wherein PCA formation isminimized.

BRIEF SUMMARY OF THE INVENTION

A method of forming an antimicrobial article according to the inventioncomprises steps of: providing a polymerizable composition; incorporatingan antimicrobially effective amount of at least onechlorhexidine-containing antimicrobial agent into the polymerizablecomposition; and, polymerizing the polymerizable composition to formchlorhexidine-containing polymer of the antimicrobial article, whereinprocessing temperature during the method is less than about 80° C. In afurther embodiment, the processing temperature during the method is lessthan about 40° C., preferably less than about 35° C. or, morepreferably, less than about 30° C. In a still further embodiment, theprocessing temperature during the method is about room temperature(i.e., 22° C.-25° C.). Preferably, to maximize benefits of theinvention, the processing temperature during the method is less thanthat temperature at which chlorhexidine decomposes to PCA.

The antimicrobially effective amount of at least onechlorhexidine-containing antimicrobial agent in the antimicrobialarticle consists essentially of chlorhexidine free base in oneembodiment. For example, in one embodiment, an antimicrobial articleprepared according to the method of the invention comprises about 10weight % chlorhexidine free base based on total weight of thechlorhexidine-containing polymer. In another embodiment, theantimicrobially effective amount of at least onechlorhexidine-containing antimicrobial agent comprises chlorhexidinesalt.

An exemplary method comprises continuously forming thechlorhexidine-containing polymer on a web. According to one aspect ofthe invention, polymerization of the polymerizable composition isinitiated using at least one radiation source selected from ultravioletradiation and electron beam radiation. According to another aspect ofthe invention, polymerization of the polymerizable composition isinitiated without use of an external source of thermal radiation. Forexample, 100% reactive chemistry is used to form thechlorhexidine-containing polymer in one embodiment.

Preferably, the polymerizable composition formed according to methods ofthe invention is essentially free of solvents. In one embodiment, thechlorhexidine-containing polymer is essentially free of unreactedsolvent.

While it may take many forms, in one embodiment, thechlorhexidine-containing polymer is a polymer film. According to oneaspect of the invention, the chlorhexidine-containing polymer is anadhesive. According to another aspect of the invention, thechlorhexidine-containing polymer is a backing for an adhesive-coatedantimicrobial article.

The chlorhexidine-containing polymer may also comprise any suitablechemistry. In one embodiment, the chlorhexidine-containing polymercomprises at least one base polymer selected from polycarbonates,polyvinyl fluorides, poly(meth)acrylates, polyurethanes, and modifiedpolymers thereof. An exemplary chlorhexidine-containing polymer ispolyurethane-based. Another exemplary chlorhexidine-containing polymeris (meth)acrylate-based.

Advantageously, PCA is minimal in antimicrobial articles preparedaccording to the method of the invention. In one embodiment, anantimicrobial article prepared according to the method of the inventionhas less than about 0.0001 mg/mL detectable PCA present in thechlorhexidine-containing polymer. In a further embodiment, anantimicrobial article prepared according to the method of the inventionhas essentially no detectable PCA present in thechlorhexidine-containing polymer.

DETAILED DESCRIPTION OF THE INVENTION

Antimicrobial articles of the invention are chlorhexidine-containing.Chlorhexidine-containing antimicrobial articles comprise anantimicrobially effective amount of chlorhexidine in its pure form(i.e., as a free base), an antimicrobially effective amount ofchlorhexidine in the form of at least one chlorhexidine salt, orcombinations thereof. Unlike widespread use of the general termchlorhexidine by those of ordinary skill in the art in referring only tothe salt form of chlorhexidine, unless specifically stated herein,reference to the general term chlorhexidine in describing the inventionherein is meant to include both the pure form and salt form ofchlorhexidine.

In one embodiment, chlorhexidine-containing antimicrobial articlescomprise at least one chlorhexidine salt. Suitable counterions forchlorhexidine in salts thereof include, but are not limited to,dihydrochloride, methosulfate, diphosphanilate, palmitate, lactate,gluconate, diacetate, and the like. An exemplary chlorhexidine salt ischlorhexidine gluconate (CHG), which is sometimes referred to by thoseof ordinary skill in the art as chlorhexidine digluconate.

In another embodiment, chlorhexidine is present in its substantiallypure form (i.e., as a free base). When using pure chlorhexidine,antimicrobial activity is typically increased as compared to use ofchlorhexidine salts. It is believed that lack of bonding betweenchlorhexidine and the polymeric composition in which it is dispersed (ascompared to the at least ionic bonding present when chlorhexidine saltsare dispersed in a polymeric composition) contributes to improvedrelease of chlorhexidine from the polymeric composition and, hence,antimicrobial effect.

Antimicrobial articles of the invention comprise any suitable polymericmaterials (also referred to herein simply as “polymers”), which can beformed into a wide variety of shapes suitable for their intendedapplication. Some applications impose more stringent requirements ondimensions or other properties of materials used than others. Forexample, optical clarity of polymeric materials is an importantconsideration when selecting polymeric materials for use in opticalapplications. As a further example, many applications require thatpolymeric materials used therein consist of single layer films havingcontrolled dimensions.

A “film” is generally understood to be a relatively thin, continuous,single layer of solid material. In contrast, many conventionally applied“coatings” do not form a continuous or uniform layer of material on anunderlying substrate. As such, once excess solvent (i.e., organicsolvent and/or water) is dried, liquid-applied coatings (e.g., vaporcoatings and ink jet-printed coatings) are often not able to bephysically separated from the supporting substrate on which they areformed so that they can be used as a stand-alone layer or as one ofmultiple layers in another application. Thus, such coating technologyhas its limitations and is generally deficient for formation ofpolymeric films.

In exemplary embodiments, polymer films formed according to methods ofthe invention are able to be physically separated from the supportingsubstrate on which they are formed so that they can be used as astand-alone layer or as one of multiple layers in antimicrobialarticles. Recognize, however, that polymer films may be formedcontiguously with or subsequently laminated to other polymer films orlayers (e.g., adhesive layers or release liners) according to furtherembodiments.

Antimicrobial articles and chlorhexidine-containing polymerizablecompositions used to form the same according to methods of the inventioncomprise any suitable material. Chemistry of materials used herein isnot limited so long as processing temperatures associated therewith fallwithin those of the present invention. Suitable chemistries may comprisepolyolefins (e.g., low density polyethylene), polyurethanes (e.g.,polyester polyurethane or polyether polyurethane), polyesters (e.g.,polyether polyester), and polyamides (e.g., polyether polyamide). In anexemplary embodiment, antimicrobial articles of the invention compriseat least one base polymer selected from polycarbonates, polyvinylfluorides, poly(meth)acrylates (e.g., a polyacrylate or apolymethacrylate), polyurethanes, and modified polymers thereof (e.g., ahybrid).

By use of the term “polymerizable,” it is to be understood that such acomposition contains components that will polymerize upon initiationusing any suitable method. The polymerizable composition may exist inone or multiple parts, depending on the nature of the componentstherein. It is also to be understood that each part of the polymerizablecomposition may itself comprise more than one premixed components.

“Polymerizable compositions” of the invention include at least twodifferent components (e.g., monomers, which can be mono-, di-,tri-functional, etc.), wherein the two components are mutually reactivewith each other via chemically different reactive moieties to form apolymeric backbone. The two components may react to form the polymericbackbone in linear, branched, and/or networked polymers. In preferredembodiments, polymerizable compositions are polymerizable using freeradical growth or similar polymerization methods capable of beinginitiated using a radiation source. For example, poly(meth)acrylates,polyurethanes, polyureas, and polyvinyls are capable of being formedaccording to the invention using such polymerization methods.

Understand that a polymerizable composition may be partially polymerizedor essentially non-polymerized. In an exemplary embodiment, each of theat least two different components forming the polymerizable compositionhas an average molecular weight that is less than about 1% of the weightaverage molecular weight of the fully polymerized composition. Inanother exemplary embodiment, each of the at least two differentcomponents forming the polymerizable composition has an averagemolecular weight that is less than about 10% of the weight averagemolecular weight of the fully polymerized composition. In yet anotherexemplary embodiment, each of the at least two different componentsforming the polymerizable composition has an average molecular weightthat is less than about 50% of the weight average molecular weight ofthe fully polymerized composition.

Exemplary polymers in antimicrobial articles formed according to methodsof the invention are polyurethane-based. For simplicity, the term“polyurethane” as used herein includes polymers containing urethane(also known as carbamate) linkages, urea linkages, or combinationsthereof (i.e., in the case of poly(urethane-urea)s). Thus,polyurethane-based compositions contain at least urethane linkages, urealinkages, or combinations thereof. Furthermore, polyurethane-basedpolymers are based on polymers where the polymeric backbone has at least80% urethane and/or urea repeat linkages formed during thepolymerization process.

Polyurethane-based polymers are prepared according to methods of theinvention by reacting components, which include at least oneisocyanate-reactive (e.g., hydroxy-functional, such as polyol) componentand at least one isocyanate-functional (e.g., polyisocyanate) component.For example, components of exemplary polymerizable compositions andwhich are useful in the formation of polyurethane-based polymersaccording to methods of the invention are described in U.S. PatentPublication No. US-2011-0241261-A1, entitled “Methods for PolymerizingFilms In-Situ Using a Radiation Source” and incorporated herein byreference in its entirety.

In order to minimize decomposition of chlorhexidine to PCA withinpolymerizable compositions during processing thereof to formantimicrobial articles, antimicrobial articles of the invention areformed using relatively low temperature processing—i.e., processing attemperatures less than 80° C., preferably at temperatures less thanabout 60° C., more preferably at temperatures less than about 40° C.,even more preferably less than about 35° C., and even more preferablyless than about 30° C. In an exemplary embodiment, processing occurs atabout room temperature—i.e., about 22° C.-25° C. If elevatedtemperatures are used at any time during processing, their duration isminimized. Preferably, however, temperatures used during processingnever, even briefly, exceed 80° C. or, when used, the preferred lowertemperature limits.

In exemplary embodiments, the polymerization of the polymerizablecomposition is initiated using at least one radiation source selectedfrom ultraviolet radiation, thermal radiation, and electron beamradiation. In one embodiment, polymerization of the polymerizablecomposition is initiated without use of an external source of thermalradiation. If needed, at least one of ultraviolet radiation and electronbeam radiation is used in one embodiment of the invention in order toinitiate polymerization of chlorhexidine-containing polymerizablecompositions when making chlorhexidine-containing antimicrobial articlesof the invention. Preferably, use of thermal radiation is minimized oreliminated during all processing of materials comprising chlorhexidinewhen forming antimicrobial articles according to methods of theinvention.

Methods of the invention can utilize continuous processing or batchprocessing. For example, continuous processing, such as web-basedpolymerization using relatively low energy ultraviolet radiation, can beused in one embodiment of the invention. As another example, batchprocessing, such as coating ultraviolet-curable composition on adiscrete substrate and irradiating the same, can be used in anotherembodiment of the invention.

A wide variety of antimicrobial articles can be formed according to thepresent invention. In an exemplary embodiment, an antimicrobial articlecomprises an adhesive-coated backing—e.g., an adhesive laminated to, orcoated on, a backing. In this embodiment, at least one of the backingand the adhesive contains chlorhexidine.

An exemplary embodiment of forming such a backing comprises 100%reactive chemistry, such as urethane-based chemistry, where no orminimal radiation (e.g., thermal, electron beam, or ultravioletradiation) is used to form the backing, which can be a continuousweb-based process or batch process.

An exemplary embodiment of forming such an adhesive comprises 100%reactive chemistry, such as (meth)acrylate-based chemistry, where no orminimal radiation (e.g., thermal, electron beam, or ultravioletradiation) is used to form the adhesive, which can be a continuousweb-based process or a batch process.

Another exemplary method of forming such an adhesive comprises usingultraviolet radiation. For example, a polymerizable adhesive compositioncomprising a thixotrope and ultraviolet polymerization initiator can beroll-coated onto a substrate and then subjected to ultraviolet radiationto polymerize the composition to an adhesive. U.S. Patent PublicationNo. US-2011-0241261-A1 describes such a useful polymerization method forthe present invention. U.S. Patent Publication No. US-2011-0137006-A1,entitled “Methods for Polymerizing Films In-Situ” and incorporatedherein by reference in its entirety, describes another usefulpolymerization method for the present invention.

According to a preferred aspect of methods of the invention, thechlorhexidine-containing polymerizable composition is essentially freeof solvents. In addition to, for example, environmental and safetyconcerns associated with solvent-based processing, solvent-basedprocessing typically entails use of elevated temperatures for effectiveremoval of excess solvent from the polymerized composition. It ispreferred that polymers in antimicrobial articles formed according tomethods of the invention are essentially free of unreacted solvent.Thus, it is preferred that the polymerizable compositions from whichthey are formed are essentially free of solvents.

The amount of PCA within an antimicrobial article formed according tomethods of the invention can be quantitatively analyzed using anysuitable analytical methodology. PCA's observed limit of detection (LOD)is 0.2 ng/mL and the limit of quantification (LOQ) is 0.3 ng/mLaccording to Agilent Technologies (“Analytical Methodology for PCADetection: Quantification of 4-Chloroaniline in Chlorhexidine Using theAgilent 1200 Series Rapid Resolution LC System Coupled with the Agilent6410B Triple Quadrupole LC/MS System,” Agilent Technologies, Inc., Mar.15, 2009, Publication Number 5990-3676EN). According to the analyticalmethod described therein, PCA present in a sample reacts with nitrousacid and α-naphthol to give a measurable red-colored derivative.

Exemplary embodiments and applications of the invention are described inthe following non-limiting examples.

EXAMPLES

Film Formation Method

Into a mixing tank with agitating blades operating at 60 Hertz, anadhesive precursor, commercially available from entrochem, inc.(Columbus, Ohio) under the trade designation, 320650, was pumped using adiaphragm pump. To the adhesive precursor and via a port in the top ofthe mixing tank, chlorhexidine was added in powder form to the desiredtotal weight percentage at a rate of from 1 to 50,000 grams/hour. Duringaddition of the chlorhexidine, the contents of the mixing tank wererecirculated from bottom to top, passing through a static mixer alongthe way. Upon addition of chlorhexidine to the desired amount, adegas/mix cycle was run for one hour and pulling a vacuum on the mixingtank to a minimum of about 66 kPa absolute pressure (i.e., about 10inches of mercury below atmospheric pressure), after which time periodthe contents of the mixing tank were immediately dispensed for coating.The contents were coated on-web at a coating line speed of 38 m/min (125ft/min) under ultraviolet lights operating at a wavelength of 350-400 nm(typically peaking at 369 nm) and having an irradiance of 20 mW/cm².Temperature during all of the above processing steps was maintained atroom temperature.

Extraction and Assay Method for Film

A 10-cm-by 10-cm-square sample of the film was placed in a glass vial,which was certified to meet or exceed EPA standards for volatiles. Tothe vial, 15 mL of tetrahydrofuran (THF) was added. The vial was thenplaced on a wrist-action shaker for at least sixteen hours. Then, 5 mLof the vial contents was diluted to a volume of 10 mL with a solution of27.6 grams monobasic sodium phosphate (0.36 weight % monobasic sodiumphosphate based on total weight of the diluent such that its molaritywas 0.115 mol/L), 10 milliliters triethylamine (1.36 weight %triethylamine based on total weight of the diluent such that itsmolarity was 0.036 mol/L), and 10 milliliters water (98.28 weight %water based on total weight of the diluent), with the diluent adjustedwith phosphoric acid to a pH of 3.0. The resulting solution was vortexedfor about fifteen seconds, after which time an aliquot thereof wasfiltered through a 0.45 μm pore size nylon filter membrane within asyringe-tip. The resulting filtrate was then analyzed for PCA analyteusing high performance liquid chromatographic (HPLC) analysis accordingto U.S. Pharmacopeial Convention standards for analysis of chlorhexidinehydrochloride in a HPLC system using an LC mode and 239-nanometerultraviolet detector. A 4.6-mm×25-cm column was used with abase-deactivated 5-μm USP Code L1 packing (i.e., octadecyl silanechemically bonded to porous silica or ceramic micro-particles as knownto those of ordinary skill in the art). The column temperature wasmaintained at 40° C. and the flow rate was maintained within the columnat the rate of 1.5 mL/min using a 50 μL injection size.

Example 1

An adhesive film prepared according to the Film Formation Method andcontaining 2 weight % chlorhexidine based on total weight of theadhesive was evaluated according to the Extraction and Assay Method forFilm described above. The evaluation was repeated for a total of 12samples of the same film. No PCA was detected.

Example 2

A sterilized adhesive film prepared according to the Film FormationMethod and containing 2 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 25 kGygamma radiation. No PCA was detected.

Example 3

A sterilized adhesive film prepared according to the Film FormationMethod and containing 2 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 25 kGygamma radiation and aged at an accelerated rate for six months accordingto ASTM Test Method F1980. No PCA was detected.

Example 4

A sterilized adhesive film prepared according to the Film FormationMethod and containing 2 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 25 kGygamma radiation and aged at an accelerated rate for twenty-four monthsaccording to ASTM Test Method F1980. No PCA was detected.

Example 5

An adhesive film prepared according to the Film Formation Method andcontaining 2 weight % chlorhexidine based on total weight of theadhesive was evaluated according to the Extraction and Assay Method forFilm described above. The evaluation was repeated for a total of 10samples of the same film. No PCA was detected.

Example 6

A sterilized adhesive film prepared according to the Film FormationMethod and containing 2 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 42 kGygamma radiation. No PCA was detected.

Example 7

A sterilized adhesive film prepared according to the Film FormationMethod and containing 2 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 42 kGygamma radiation. No PCA was detected.

Example 8

A sterilized adhesive film prepared according to the Film FormationMethod and containing 2 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 42 kGygamma radiation and aged in real time for two months. No PCA wasdetected.

Example 9

An adhesive film prepared according to the Film Formation Method andcontaining 10 weight % chlorhexidine based on total weight of theadhesive was evaluated according to the Extraction and Assay Method forFilm described above. The evaluation was repeated for a total of 8samples of the same film. No PCA was detected.

Example 10

A sterilized adhesive film prepared according to the Film FormationMethod and containing 10 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 43 kGygamma radiation. No PCA was detected.

Example 11

An adhesive film prepared according to the Film Formation Method andcontaining 10 weight % chlorhexidine based on total weight of theadhesive was evaluated according to the Extraction and Assay Method forFilm described above. The evaluation was repeated for a total of 12samples of the same film. No PCA was detected.

Example 12

A sterilized adhesive film prepared according to the Film FormationMethod and containing 10 weight % chlorhexidine based on total weight ofthe adhesive was evaluated according to the Extraction and Assay Methodfor Film described above. The evaluation was repeated for a total of 12samples of the same film. Each sample was sterilized to a dose of 43 kGygamma radiation and aged at an accelerated rate for twelve monthsaccording to ASTM Test Method F1980. No PCA was detected.

Comparative Example C1

Wound dressing film containing chlorhexidine and commercially sold byCovalon Technologies Ltd. of Mississauga, Ontario, Canada as SURGICLEARAntimicrobial Clear Silicone Surgical Dressing was evaluated about sixmonths before its expiration date according to the Extraction and AssayMethod for Film described above. The evaluation was repeated for a totalof 4 samples of the same film. PCA in the amount of 0.0001 mg/mL wasdetected in each of the samples.

Various modifications and alterations of the invention will becomeapparent to those skilled in the art without departing from the spiritand scope of the invention, which is defined by the accompanying claims.It should be noted that steps recited in any method claims below do notnecessarily need to be performed in the order that they are recited.Those of ordinary skill in the art will recognize variations inperforming the steps from the order in which they are recited. Inaddition, the lack of mention or discussion of a feature, step, orcomponent provides the basis for claims where the absent feature orcomponent is excluded by way of a proviso or similar claim language.

Further, as used throughout, ranges may be used as shorthand fordescribing each and every value that is within the range. Any valuewithin the range can be selected as the terminus of the range.Similarly, any discrete value within the range can be selected as theminimum or maximum value recited in describing and claiming features ofthe invention.

In addition, as discussed herein it is again noted that compositionsdescribed herein may comprise all components in one or multiple parts.Further, while reference may be made herein to preparation of thevarious intermediate components, recognize that some such intermediatecomponents may be commercially available and, as such, can be usedaccording to the invention as an alternative to otherwise preparing thesame. Other variations are recognizable to those of ordinary skill inthe art.

1. (canceled)
 2. The chlorhexidine-containing polymer of claim 19,wherein the processing temperature during the method is less than about40° C.
 3. The chlorhexidine-containing polymer of claim 19, wherein theprocessing temperature during the method is about room temperature. 4.The chlorhexidine-containing polymer of claim 19, wherein the processingtemperature during the method is less than that temperature at whichchlorhexidine decomposes to para-chloroaniline.
 5. Thechlorhexidine-containing polymer of claim 19, wherein theantimicrobially effective amount of at least onechlorhexidine-containing antimicrobial agent in the antimicrobialarticle consists essentially of chlorhexidine free base.
 6. Thechlorhexidine-containing polymer of claim 19, wherein theantimicrobially effective amount of at least onechlorhexidine-containing antimicrobial agent comprises chlorhexidinesalt.
 7. The chlorhexidine-containing polymer of claim 19, whereinmethod comprises continuously forming the chlorhexidine-containingpolymer is formed on a web.
 8. (canceled)
 9. Thechlorhexidine-containing polymer of claim 19, wherein thechlorhexidine-containing polymer is essentially free of unreactedsolvent.
 10. (canceled)
 11. The chlorhexidine-containing polymer ofclaim 19, wherein polymerization of the polymerizable composition isinitiated without use of an external source of thermal radiation. 12.The chlorhexidine-containing polymer of claim 19, wherein thechlorhexidine-containing polymer is in the form of a polymer film. 13.The chlorhexidine-containing polymer of claim 19, wherein thechlorhexidine-containing polymer is an adhesive.
 14. Thechlorhexidine-containing polymer of claim 19, wherein thechlorhexidine-containing polymer is a backing for an adhesive-coatedantimicrobial article.
 15. (canceled)
 16. The chlorhexidine-containingpolymer of claim 19, wherein the chlorhexidine-containing polymercomprises at least one base polymer selected from polycarbonates,polyvinyl fluorides, poly(meth)acrylates, polyurethanes, and modifiedpolymers thereof.
 17. The chlorhexidine-containing polymer of claim 19,wherein the chlorhexidine-containing polymer is polyurethane-based. 18.The chlorhexidine-containing polymer of claim 19, wherein thechlorhexidine-containing polymer is (meth)acrylate-based.
 19. Achlorhexidine-containing polymer prepared according to a methodcomprising steps of: providing a polymerizable composition;incorporating an antimicrobially effective amount of at least onechlorhexidine-containing antimicrobial agent into the polymerizablecomposition; and, polymerizing the polymerizable composition to form thechlorhexidine-containing polymer, wherein processing temperature duringthe method is less than about 80° C.
 20. An antimicrobial articlecomprising at least one chlorhexidine-containing polymer, wherein lessthan about 0.0001 mg/mL detectable para-chloroaniline is present in thechlorhexidine-containing polymer.
 21. The antimicrobial article of claim20, wherein the article comprises about 10 weight % chlorhexidine freebase based on total weight of the chlorhexidine-containing polymer. 22.The antimicrobial article of claim 20, wherein essentially no detectablepara-chloroaniline is present in the chlorhexidine-containing polymer.23. The chlorhexidine-containing polymer of claim 19, wherein the stepof providing a polymerizable composition consists of providing apolymerizable composition comprising at least two different components,wherein each of the at least two different components are mutuallyreactive with each other via chemically different reactive moieties toform a polymeric backbone, and wherein each of the at least twodifferent components has an average molecular weight that is less thanabout 10% of the weight average molecular weight of the fullypolymerized composition.
 24. The chlorhexidine-containing polymer ofclaim 19, wherein chemistry of the chlorhexidine-containing polymer isselected from the group consisting of polyolefins, polyurethanes,polyesters, and polyamides.
 25. An antimicrobial article comprising thechlorhexidine-containing polymer of claim 19.